Although the ultimate goal of this project is the development of specific modes of immunosuppression capable of promoting long term allograft survival with minimal side effects, elucidation of the structure and function of molecules involved in the cytolytic T lymphocyte (CTL) response represents an essential step towards this goal. For the past three years, we have studied lymphocyte function-associated antigens as defined by monoclonal antibodies which inhibit lymphocyte function. We propose here to expand these studies to antigens expressed by interleukin 2 (IL-2) dependent, antigen specific functional cytolytic T lymphocyte lines but which are not expressed by cells of other lineages or states of differentiation. Three complementary approached will be used to identify molecules limited to fully differentiated T cells: 1) subtractive absorption of polyspecific antisera; 2) subtractive immunization using tolerizing doses of anti-L3T4 antibody plus cellular antigen; and 3) substrative hybridization to identify T cell specific cDNA clones. The molecules so identified will be studied with regard to structure and function using the techniques of cellular immunology, protein chemistry, and molecular biology. The reagents and strategies so devised should prove useful as diagnostic and immunotherapeutic agents in organ transplantation.